Peripheral and cerebrospinal fluid immune activation and inflammation in chronically HIV-infected patients before and after virally suppressive combination antiretroviral therapy (cART)
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Cerebrospinal fluid (CSF)/plasma HIV-RNA ratio has been associated with residual neurocognitive impairment on cART, leading us to hypothesize a specific peripheral and/or CSF immune feature in patients with high CSF/plasma ratio (≥ 1). In patients with diverse pre-cART CSF/plasma ratio (61/70 with CSF/plasma ratio < 1, L-CSF, 9/70 with CSF/plasma ratio ≥ 1, H-CSF), we investigated the effects of 12 months of effective cART on peripheral and CSF inflammatory markers, on T cell activation/maturation and HIV/CMV-specific intracellular cytokine pattern. We also studied the possible clinical association between peripheral/CSF pro-inflammatory milieu and neurocognitive screening tests (MMSE, FAB, IHDS). Prior to cART, the two groups were comparable for peripheral and CSF inflammation, T cell activation/proliferation and maturation, and HIV/CMV-specific response. Upon cART initiation, both H-CSF and L-CSF featured a significant reduction in plasma TNF-α and circulating CD8 activation, with a redistribution of memory/naïve T cell subsets in L-CSF alone. In the CSF compartment, cART seemed able to reduce pro-inflammatory cytokine/chemokine levels in both H-CSF and L-CSF patients. Interestingly, despite a reduction in the pro-inflammatory milieu, no changes were shown in neurocognitive screening tests in both patients’ groups. We hereby show that 12-month cART is able to reduce intratechal and peripheral pro-inflammatory burden; a longer cART exposure and a more comprehensive neuropsychological evaluation might be necessary to gain a broader insight into the possible effects on neurocognitive performance.
KeywordsCSF/plasma HIV-RNA ratio HIV-associated neurocognitive disorders Peripheral immune activation CSF inflammatory markers
We thank all of the patients who participated in the study and the staff of the Clinic of Infectious Diseases and Tropical Medicine at “ASST Santi Paolo e Carlo”, Milan and of Amedeo di Savoia Hospital, Turin who cared for the patients. Presented in part at 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Vancouver, B.C., Canada (19-22 July2015). Oral Poster #TUPDA0101.
This study was supported by Gilead Fellowship 2012 grant number F61bd8c044 to G.M.
Compliance with ethical standards
Ethics approval and consent to participate
The ethics committee of the Clinic of Infectious Diseases, University of Milan-ASST Santi Paolo e Carlo, Milan and of Amedeo di Savoia Hospital, Turin (Italy) approved this study. All subjects gave written informed consent in accordance with the Declaration of Helsinki.
Conflict of interest
E.M., F.I., A.C., F.B., M.T., A.D.M., and S.B. declare that they have no conflict of interests. G.M. received research grant by Gilead.
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